Pharmacokinetics of 5-Fluorouracil in Rabbits in Experimental Regional Chemotherapy

Rita Kar, Robert A. Cohen, Theresa M. Terem, Maurice Y. Nahabedian

Research output: Contribution to journalArticlepeer-review

Abstract

The goal of this study was to identify the mode(s) of regional administration of 5-fluorouracil (5-FUra) with the greatest pharmacological advantage in an animal model. Parameters examined were the amount of systemic exposure to 5-FUra and plasma and tissue levels of 5-FUra. Anesthetized New Zealand white rabbits bearing a VX-2 carcinoma in the thigh received 5-FUra (20 mg/kg body weight) by the following routes: i.v., intraarterial (i.a.), i.a. with stopflow, i.a. with outflow occlusion, and isolation perfusion (IP). Serial venous blood samples were obtained prior to and after drug administration for a total of 45 min. A similar sampling of the perfusion circuit was conducted in those animals undergoing IP. At the end of the sampling period tumor and adjacent normal muscle were obtained. Plasma and tissue levels of 5-FUra were determined by a high pressure liquid chromatographic method. It was observed that systemic exposure to 5-FUra was identical for the i.v., i.a., i.a. with stopflow, and i.a. with outflow occlusion groups. Systemic exposure to 5-FUra in the IP group was only 0.30 of that observed for the i.a. group. Tissue 5-FUra levels in the i.v., i.a., and i.a. with stopflow groups were low and comparable to one another. Tissue levels of the 5-FUra were significantly higher in the i.a. with outflow occlusion and IP groups. We conclude that only selected forms of regional administration of 5-FUra offer pharmacological advantage when compared to systemic administration.

Original languageEnglish (US)
Pages (from-to)4491-4495
Number of pages5
JournalCancer Research
Volume46
Issue number9
StatePublished - Sep 1986

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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